We have previously demonstrated that cyclic guanosine monophosphate (cGMP) inhibits renal cortical production of glucose and ammonia in vitro. Further, we have found that metabolic acidosis decreases and alkalosis increases the concentration of cGMP in renal cortex, lung and plasma of rats. We have suggested that these changes in cGMP may play a role in mediating the effect of acid-base changes on renal production of ammonia and glucose, and may play a role in the metabolic processes presumably involved in cellular buffering of acid and alkali loads. In our proposed work we will study further the effects of acidosis, alkalosis, and related abnormalities on cyclic GMP, guanyl cyclase activity, and degradation of cyclic GMP in a number of tissues. We also propose to apply an immunofluorescent technique to locate the site of change of cyclic GMP in cortex and lung in acidosis and alkalosis.